{
  "abstract": "The human complement system is a protein network in blood and other body fluids that fights invading pathogens and is involved in maintaining homeostasis. A central step in the complement cascade is the conversion of complement protein C3 to C3b by convertase enzymes. Upon cleavage of C3, the nascent C3b molecule undergoes a large conformational change which exposes new epitopes. Molecules that discriminate between C3b and C3 could provide a powerful tool to selectively bind surface-bound complement activation products while leaving the circulating precursors untouched. In this study, we developed C3b-specific nanobodies by generating phage libraries from llamas immunized with purified and surface-bound C3b. We describe UNbC3b-1 as a high-affinity binder that recognizes soluble and surface-bound C3b molecules but does not bind to C3 in its native state. A 4.2 [A] structure of the UNbC3b-1:C3b complex generated by cryogenic electron microscopy shows that UNbC3b-1 binds C3b at the interface of MG3, MG4, and MG6, overlapping with the complement receptor immunoglobulin (CRIg) binding site. Functionally, we show that UNbC3b-1 inhibits complement activity in the alternative pathway (AP), likely by preventing association between substrate C3 and the AP C3 convertase (C3bBb). Altogether, nanobody UNbC3b-1 is a valuable tool to specifically bind C3b molecules and to selectively inhibit the AP convertases of the complement system.",
  "abstract_shown": true,
  "affiliations": [
    "University Medical Center Utrecht"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "E. M. Struijf"
    },
    {
      "name": "B. W. Bardoel"
    },
    {
      "name": "J. E. van Keulen"
    },
    {
      "name": "M. Ruyken"
    },
    {
      "name": "D. Y. Siere"
    },
    {
      "name": "D. J. Dijkstra"
    },
    {
      "name": "G. Dekkers"
    },
    {
      "name": "P. Gros"
    },
    {
      "name": "R. Heukers"
    },
    {
      "name": "D. A. C. Heesterbeek"
    },
    {
      "name": "S. H. M. Rooijakkers"
    },
    {
      "affs": [
        0
      ],
      "name": "J. S. Depelteau"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ekssgmgq4010d.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.30.748118",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.30.748118v1.full",
  "id": "ekssgmgq4010d",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.30.748118v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|Complement system in diseases"
    ]
  ],
  "openalex": "W7208708557",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.30.748118v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ekssgmgq4010d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "10.64898/2026.08.30.748118",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.30.748118v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Identification of a C3b-specific nanobody that does not bind C3 and blocks alternative pathway convertases",
  "title_text": "Identification of a C3b-specific nanobody that does not bind C3 and blocks alternative pathway convertases",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/ekssgmgq4010d",
  "venue": "bioRxiv",
  "versions": []
}